• Multidrug and toxic compound extrusion (MATE) proteins comprise the most recently identified family of multidrug transporters. In plants, the numbers of MATE proteins has undergone a remarkable expansion, underscoring the importance of these transporters within this kingdom. • Here, we describe the identification and characterization of Activated Disease Susceptibility 1 (ADS1) which encodes a putative MATE transport protein. An activation tagging screen uncovered the ads1‐Dominant (ads1‐D) mutant, which was subsequently characterized by molecular, genetic and biochemical approaches. • The ads1‐D mutant was compromised in both basal and nonhost resistance against microbial pathogens. Further, plant defence responses conferred by RPS4 were also disabled in ads1‐D plants. By contrast, depletion of ADS1 transcripts by RNA‐interference (RNAi) promoted basal disease resistance. Unexpectedly, ads1‐D plants were found to constitutively accumulate reactive oxygen intermediates (ROIs). However, analysis of ads1‐D Arabidopsis thaliana respiratory burst oxidase (atrboh) double and triple mutants indicated that an increase in ROIs did not impact ads1‐D‐mediated disease susceptibility. • Our findings imply that ADS1 negatively regulates the accumulation of the plant immune activator salicylic acid (SA) and cognate Pathogenesis‐Related 1 (PR1) gene expression. Collectively, these data highlight an important role for MATE proteins in the establishment of plant disease resistance.